Introduction
Transgender and gender diverse (TGD) adolescents are those whose gender identity differs from their sex assigned at birth ( Table 3.1 ). Although the prevalence of gender diversity in the population is difficult to ascertain because of poor data collection at the national level, roughly 0.5% of adults are estimated to identify as transgender, with 1.3% of 18- to 24-year-olds and 1.4% of 13- to 17-year-olds. As such, it is likely that all clinicians will provide care for TGD adolescents at some point in their career. Much of the specific medical and surgical care that TGD adolescents may seek is within the domain of pediatric and adolescent gynecology, including hormone therapy, fertility counseling, sexual health, and reproductive surgeries. This chapter provides an overview of gender-affirming care as it relates to the field. Additional resources are provided in Table 3.2 .
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World Professional Association for Transgender Health (WPATH) Standards of Care
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The Endocrine Society Guidelines on the Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons
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University of California San Francisco Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People.
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Barriers to care
TGD individuals face numerous systemic and specific health care barriers. Many are grounded in the roots of inequities. TGD individuals continue to face widespread societal discrimination, including in terms of education, housing, and employment discrimination; ostracization from families; and targeted exclusion from social spaces and activities as well as targeted violence. These disparities are further heightened for those who are also persons of color. In large part, as a result of these, TGD individuals have higher rates of mental health and chronic health disparities, being unable to obtain comprehensive insurance, experiencing homelessness, and living below the poverty line. , The 2015 US Transgender Survey found that one in four individuals experienced some degree of discrimination, violence, or refusal of necessary care because of being TGD, and one in three would delay or avoid engaging with health care because of fear of said concerns. In reproductive health care settings, there are additional barriers and layers of discrimination. Many gynecologic spaces assume all individuals have the same sex traits and the same gender. Some gynecologists refuse to provide care to transgender men and transmasculine individuals who have anatomy and physiologic needs within gynecology but who are not women. Additionally, some gynecologists refuse to provide care for transgender women or transfeminine individuals who, although they identify as women, may have anatomy that differs from what gynecologists have training and familiarity with. TGD individuals have documented concerns with the gendered nature of gynecology and seek competent and welcoming care. Similarly, surveys of clinicians in obstetrics and gynecology find that few physicians feel prepared to care for TGD individuals. Collectively, these chasms in care knowledge of the clinician, crossed with the experiences and preferences of TGD individuals, unite to support the call for more clinicians to be trained in culturally inclusive and competent care for TGD individuals.
Many clinicians see TGD individuals for the routine spectrum of care they provide for their cisgender patients, such as for menstrual suppression or vaginal discharge. As such, clinicians may not know a patient who is TGD is scheduled until they are seeing the patient. There are certain things that clinicians should employ universally to ensure that no assumptions are made about which of their patients are cisgender and which are TGD. All patients should be asked about their name in use and pronouns, and this information should be documented in a place that is universally accessible to all clinical staff. Clinics should review their environment to ensure it is reflective of the populations they serve, including diverse posters, magazines, and handouts. Signage that specifically welcomes LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and more) individuals, such as rainbows or trans flags, can signal safety to TGD patients. For patients who are presenting seeking gender-affirming hormone therapies or surgeries, the initial visit should additionally include discussions about gender identity, history of gender exploration, any social transition that has occurred (e.g., name change), and any gender-related goals (including any physical changes desired). , Patients should be asked about their desired timing for these changes and about their reasoning for timing so that clinicians can understand the patients’ longitudinal plan.
How to Take an Embodiment-Centered Approach to Gender Care- •
Rather than asking which therapies or surgeries a patient is seeking, ask about the specific changes or goals they are seeking.
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Explore which, if any, therapies might help them best achieve these goals.
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Fertility
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Family building
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Fertility preservation options
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Genital changes
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Sexual experience changes
Remove the assumption from clinicians that all TGD individuals of the same gender desire the same therapies and goals, and instead create a system where patients are offered therapies that best address their individual goals.
Adolescence can also be a tumultuous time in life, and in accordance with general pediatric goals, all patients who are experiencing psychosocial concerns should be connected with mental health resources; TGD adolescents are no exception. For those who are desiring hormonal or surgical therapies, mental health clinicians are recommended to be involved in care by national and international guidelines, and as such, clinicians should aid TGD patients in networking to find a TGD-inclusive mental health provider. ,
Puberty suppression
Puberty marks a particularly crucial time in the management of children and adolescents with gender dysphoria, as the unwanted physical changes that accompany puberty put them at the high risk of adverse mental health outcomes. As previously stated, TGD youth are not only at a higher risk of suicide, substance abuse, and high-risk sexual behavior; they also comprise a disproportionate portion of the homeless population. After the mental health provider has determined that the adolescent has met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for gender dysphoria, the Endocrine Society guidelines support the use of puberty blockers starting when the youth reaches Tanner stage 2 of puberty. This typically consists of breast budding in those assigned female at birth and reaching testicular volume of 4 cc in those assigned male. Initiating treatment to suppress these pubertal changes not only minimizes the mental distress brought about by puberty but also prevents the development of secondary sexual characteristics that may later be difficult to address, such as the sound of the voice, the Adam’s apple, or large breasts.
Puberty suppression is typically achieved with the use of gonadotropin-releasing hormone (GnRH) analogues. This includes depot leuprolide acetate and the Histrelin implant. The suppression of pubertal changes allows the adolescents to engage with a mental health provider and explore their gender identity before engaging in gender-affirming medical and surgical interventions that have permanent effects. Puberty suppression is reversible, and in the event that treatment is discontinued, endogenous puberty will ensue.
Follow-up and monitoring
Although puberty suppression is considered reversible, the effects of GnRH analogues on bone mineral density in adolescents are not completely known. Thus testing for bone mineral density annually is recommended by the Endocrine Society. Calcium and vitamin D supplementation may be offered to adolescents undergoing pubertal suppression, and physical activity and weight-bearing exercise should be encouraged. The Endocrine Society also recommends evaluation of gonadotropins (luteinizing hormone/follicle-stimulating hormone [LH/FSH]) as well as testosterone or estradiol levels every 3 months, along with height and weight measurements and Tanner staging during each visit.
Special considerations
Transmasculine adolescents who start gender-affirming therapy at or beyond puberty may opt to forego pubertal suppression. Menstrual suppression may also be considered. Although cessation of menstruation can be expected within the first few months of testosterone use, those who are on neither puberty-suppressing nor testosterone treatment should be offered menstrual suppression should menses be a significant cause of distress. Any agent that can be used to suppress periods in cisgender female adolescents can be considered; however, many transmasculine individuals may prefer methods without estrogen. Systemic progesterone—in the form of oral, depo, intrauterine, or an implant—can be considered in those wishing menstrual suppression without additional estrogen exposure. Progesterone-containing intrauterine devices specifically decrease menstrual flow or fully suppress periods.
TGD adolescents should receive ongoing counseling regarding their options for fertility preservation throughout their gender-affirming care; however, this is especially true in adolescents seeking puberty suppression. GnRH analogue treatment results in cessation of germ cell maturation, and at this time there are no options for fertility preservation in children and adolescents who have not undergone puberty in their gender assigned at birth. Providers should engage adolescents in discussions regarding their fertility and their options for fertility preservation before pubertal suppression and before the use of testosterone or estrogen (see Chapter 27 ). Menstrual Suppression Please refer to Appendix 3.1 for patient friendly handout reviewing all the options.
Gender-affirming hormones
The Endocrine Society guidelines support the initiation of testosterone or estrogen around the age of 16, when adolescents are known to have the sufficient capacity to provide informed assent. Although data surrounding the use of gender-affirming hormones before age 13.5 to 14 years are limited, special consideration can be given to adolescents before the age of 16 in cases where there is compelling support from both their medical and mental health providers.
Written documentation from a dedicated mental health professional about the patient’s eligibility and need for gender-affirming treatment was strongly recommended in the past by the prior World Professional Association for Transgender Health (WPATH) Standards of Care version 7; however, this presented a challenge to adolescents receiving gender-affirming care in a timely manner. Although gender-affirming care is best undertaken in a multidisciplinary environment, not all TGD youth and their families have access to such care. In settings where multiple disciplines are available and accessible to patients, all relevant providers should be included in the provision of gender-affirming care to adolescents. Any written documentation recommending gender-affirming care should include assessments from both medical and mental health providers. There are cases where parental consent is not required to receive gender-affirming care; however, obtaining consent is preferable, as parental support improves clinical outcomes during hormone therapy.
Adolescents and their families should be made aware of the possible health effects of both masculinizing and feminizing therapy, and expectations should be set as to the timing and extent of the physical changes brought about by gender-affirming medications. Providers should be aware that although surgery can be an important component in the treatment of gender dysphoria, hormone therapy serves as the endpoint for many individuals, especially if surgery is not consistent with their goals toward their gender identity.
Masculinizing therapy
Testosterone is available as injectable esters for adolescents seeking masculinizing therapy. It can also be administered transdermally in the form of patches and gels and subcutaneously as pellets. Parenteral formulations, administered either subcutaneously or intramuscularly, are typically recommended during puberty induction because of the low cost and ease of self-administration. Puberty induction with testosterone in transmasculine adolescents typically starts at 25 mg every 7 to 14 days, increasing incrementally every 3 to 6 months to an adult maintenance dose of 50 to 100 mg every week. After puberty induction, testosterone levels are typically maintained within physiologic levels for males (400–700 ng/dL), although it is unclear what the optimal ranges are in transmasculine patients. Desired effects of testosterone include virilization of the body and development of male secondary sex characteristics, including growth of facial and body hair, lowering of the voice, and increase in muscle development. Given the partially irreversible nature of these changes, the Endocrine Society recommends gradual and incremental dosing of testosterone regardless of whether or not puberty suppression was undertaken before starting androgen therapy.
Clinical monitoring of their pubertal development as well as laboratory evaluation is also recommended every 3 to 6 months during treatment, including sex steroid hormone levels and complete blood counts. This allows for close monitoring for adverse effects secondary to therapy ( Table 3.2 ). Of particular concern is erythrocytosis secondary to testosterone, although hypertension and hyperlipidemia can occur with long-term use as well. The decision regarding the frequency and breadth of surveillance should be individualized to each adolescent’s comorbidities, lifestyle risks, and response to treatment. There is no evidence to suggest standardized testing intervals while undergoing treatment.
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Feminizing therapy
Feminizing therapy typically involves estrogen and antiandrogens, especially in patients who have not undergone puberty suppression. 
Estrogen alone has been shown to be insufficient in the suppression of testosterone when administered at physiologic doses, so adjunctive therapy is typically required to achieve testosterone levels in the female range. Puberty induction with estrogen is typically initiated with oral formulations and transdermal estradiol, although parenteral formulations are also available for maintenance in older adolescents and adults. In adolescents undergoing puberty induction with oral formulations, estrogen treatment may begin with 1 mg daily dosing, incrementally increasing to typical adult maintenance doses of 4 to 6 mg daily every 3 to 4 months. Similarly, puberty induction with transdermal estrogen may start with the 0.1 mg/day patch, which can then be incrementally increased to up to a 0.4 mg/day dose. Serum estradiol levels are maintained at the level for premenopausal females (100–200 pg/mL), whereas testosterone levels are ideally suppressed below 50 ng/dL. Physical changes secondary to feminizing therapy are typically evident within the first 3 to 12 months, including increased breast tissue growth, redistribution of fat mass to the hips and thighs, and decreased facial and body hair. Similar to masculinizing therapy, these physical changes are partially irreversible; thus initiation of therapy is typically undertaken with a gradually increasing schedule.
Providers should be aware of a number of antiandrogen and progestin medications transfeminine adolescents may use as adjunctive therapy to estrogen. The most common antiandrogen is spironolactone, which works by blocking the action of testosterone at the level of the androgen receptors. This results in a reduction in the rate of growth and thickness of male-pattern hair. The addition of antiandrogenic medications also allows for the reduction of testosterone levels toward the preferred physiologic levels as well as the reduction of the amount of estrogen needed to achieve the desired physical effects. Spironolactone is a weak antihypertensive; thus providers should be aware of the potential for hypokalemia and reduced blood pressure. Current WPATH guidelines recommend regular assessment of renal function and potassium levels in conjunction with spironolactone use. Alternative antiandrogens include finasteride, bicalutamide, and GnRH analogues. Some adolescents may also opt for progestin therapy in addition to estradiol in hopes of potentiating the breast growth brought about by estrogen; however, the evidence to support this practice is very limited.
As with masculinizing therapy, regular clinical and laboratory assessment is recommended every 3 to 6 months to prevent potential adverse events during treatment with estradiol ( Table 3.3 ). Exogenous estrogen is known to increase the risk of venous thromboembolism, although this risk can be minimized by maintaining levels within the desired physiologic range and with the use of transdermal formulations. There is also a risk of liver dysfunction, hypertension, and hyperprolactinemia, so appropriate monitoring should be undertaken, especially in adolescents at higher doses.
